Made available in DSpace on 2014-06-11T19:35:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-08-24Bitstream added on 2014-06-13T20:06:20Z : No. of bitstreams: 1 hatschbach_e_dr_botfm.pdf: 353236 bytes, checksum: 3540e90d79e3d99755eddf9db2abf5c2 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A anestesia venosa total possui muitas vantagens, não polui ar ambiente, fácil de usar em lugares remotos, estabilidade cardiovascular e boa qualidade de recuperação. O propofol, devido sua farmacologia, é um dos fármacos mais usados em infusões contínuas. Recentes avanços têm acontecido na anestesia venosa total com a utilização de infusões alvo controlada, baseados em simulações farmacodinâmicas e farmacocinéticas dos fármacos em tempo real, inclusive na Medicina Veterinária. Em função disso, pretendeu-se colocar em prática este tipo de anestesia, utilizando-a em cadelas para a realização de cirurgias de ovariosalpingohisterectomia. Para isso foram anestesiadas 20 cadelas, após o consentimento livre e esclarecido dos proprietários. Sendo divididos em dois grupos (GI e GII). Em GI, os animais foram pré-tratados com levomepromazina na dose de 0,5mg/kg IV e anestesiados com propofol por infusão alvo controlada na dose de indução de 3,5æg/ml e na dose de manutenção de 1,5 æg/ml IV, através bomba de infusão Harvard pump, associado com remifentanila na dose de 0,3æg/kg/min, através de bomba de seringa. Em GII, os animais receberam o mesmo tratamento de GI, só que ao invés de receberem o propofol por infusão alvo controlada, receberam o propofol a 5mg/kg como dose de indução e como manutenção, receberam o propofol em infusão contínua de velocidade fixa, na dose de 0,2mg/kg/min. Assim, compararam-se as duas técnicas de infusão, a de velocidade fixa e a alvo controlada, concluindo-se que as doses de propofol utilizadas em ambas as técnicas, após o pré-tratamento de levomepromazina e associadas ao opióide, foram eficazes para a realização cirúrgica, promovendo bradicardia e discreta hipotensão, porém estabilidade hemogasométrica e respiratória... / Total venous anesthesia has many advantages as it does not pollute environmental air, can be easily used in remote sites, provides cardiovascular stability and good recovery quality. Due to its pharmacology, propofol is one of the most frequently used drugs in continuous infusions. Recently, advances have also been observed in total venous anesthesia with the use of target-controlled infusions based on real-time pharmacodynamic and pharmacokinetic drug simulations in Veterinary Medicine. As a result, this study aimed at applying this type of anesthesia by using it in female dogs for the performance of ovariosalpingohysterectomy surgery. To that end, twenty female dogs were anesthetized after free consent was given by their owners. The animals were divided into two groups (GI and GII). In GI, the dogs were pre-treated with methotrimeprazine at a dose of 0.5mg/kg IV and anesthetized with propofol by target-controlled infusion at an induction dose of 3.5æg/ml and a maintenance dose of 1.5 æg/ml IV by means of a Harvard infusion pump associated with remifentanil at a dose of 0.3æg/kg/min by means of a syringe pump. In GII, the animals received the same treatment as that given to GI, except that instead of receiving propofol by target-controlled infusion, they were given propofol at 5mg/kg as an induction dose. As maintenance, they received propofol by single-speed continuous infusion at a dose of 0.2mg/kg/min. Hence, two infusion techniques, fixed-speed infusion and target-controlled infusion, were compared, leading to the conclusion that the doses of propofol used in both techniques, after pre-treated with methotrimeprazine, associated with the opioid were efficient for surgery performance as they promoted bradycardia and discreet hypotension, but hemogasometric and respiratory stability, futher good muscle relaxation, more evident in fixed-speed infusion... (Complete abstract click electronic access below)

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Dehydrated or hypovolemic patients need electrolyte and blood volume expanders replacement. Besides the care to make adequate volume, especially in critically ill patients, it is essential that the rate of replacement is faithful to the calculation designed. This study aimed to evaluate, in vitro, flow catheters of different diameters of four trade-mark available in market, more used for fluidtherapy in domestic animals at the Veterinary Teaching Hospital of the Federal University of Santa Maria (UFSM). There were used bottles of 500 and 1000 mL of 0.9% saline solution and macrodrops intravenous set from the same brand. With this research it was concluded that the average flow of catheters does not match the data released on the sales packaging thereof; even though the same number, the flow rate varies with the brand of the catheter. The use of the infusion pump in cases of shock only provides the flow necessary for dogs up to 11.1kg. / Pacientes desidratados ou hipovolêmicos requerem reposição hidroeletrolítica e de expansores da volemia. Além do cuidado para se efetuar adequado volume, especialmente em pacientes críticos, é fundamental que a velocidade de reposição seja fiel ao cálculo projetado, dessa forma, este estudo teve como objetivo avaliar, in vitro, a vazão de cateteres de diferentes diâmetros de quatro marcas comerciais, mais utilizados na fluidoterapia dos animais domésticos no Hospital Veterinário Universitário da Universidade Federal de Santa Maria (UFSM), utilizando frascos de 500 e 1000mL de solução fisiológica 0,9% de uma mesma marca e equipo macrogotas. Com este trabalho conclui-se que a vazão média dos cateteres não corresponde aos dados divulgados na embalagem, nos diferentes diâmetros e diferentes marcas comerciais; a utilização da bomba de infusão em casos de choque só fornece a vazão necessária para cães até 11,1kg.

Made available in DSpace on 2014-06-11T19:23:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-11-06Bitstream added on 2014-06-13T18:51:11Z : No. of bitstreams: 1 marqueti_ps_me_jabo.pdf: 824420 bytes, checksum: 0961ad61a6416f733c5a56c8c5183588 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Foram utilizados 20 suínos machos ou fêmeas, distribuídos aleatoriamente em dois grupos experimentais, grupo 1 (G1) e grupo 2 (G2). Empregouse como medicação pré-anestésica (MPA) azaperona 1,0 mg/kg e midazolam 0,2 mg/kg, administrados por via intramuscular, nos animais de ambos os grupos. Decorridos 15 minutos da aplicação da MPA, aos animais dos grupos 1 e 2, procedeuse a indução anestésica com propofol na dose de 4,0 mg/kg, via intravenosa, mantendo-se por infusão contínua, por via intravenosa, propofol na dose de 0,4 mg/kg/minuto, durante uma hora. Aos animais do G2, administrou-se um “bolus” de tramadol na dose de 4,0 mg/kg, por via intravenosa, logo após a indução anestésica com propofol. Avaliaram-se as freqüências cardíaca e respiratória, temperatura retal, sedação, intubação orotraqueal, analgesia, pressões arteriais (sistólica, diastólica e média), saturação da oxihemoglobina, reflexos protetores, dosagem de cortisol e recuperação (tempo de extubação, tempo para decúbito esternal, tempo para posição quadrupedal), entre os grupos, dentro de cada momento. As freqüências cardíaca e respiratória e a dosagem de cortisol apresentaram diferenças significativas (P<0,05) entre os momentos. A temperatura retal apresentou efeito significativo (P<0,05) da interação entre grupo e momento. As pressões arteriais (sistólica, diastólica e média) apresentaram diferenças significativas (P<0,05) entre grupos e momentos. Os reflexos protetores (ocular, palpebral e anal), apresentaram diferenças significativas (P 0,05) entre os grupos, assim como o tempo de extubação, um dos parâmetros de recuperação. Sedação, intubação orotraqueal, analgesia, saturação de oxihemoglobina, tempo para decúbito esternal e tempo para posição quadrupedal não apresentaram diferenças significativas (P>0,05) entre os grupos e nem entre momentos. / Twenty swines were used, among males or females, both duly spreaded over randomly performed, in two experimental groups: group 1 (G1) and group 2 (G2). The pre-anesthesic medication made up of an association of azaperone 1,0 mg/kg and midazolam 0,2 mg/kg, together IM, was common to both groups. After 15 minutes of the application of the pre-anesthesic medication, to the animals of the groups 1 and 2, the anesthesic induction with propofol was proceeded on the basis of 4,0 mg/kg, intravenous via, keeping a the a continuous intravenous infusion with the same drug, on the basis of 0,4 mg/kg/min, during the period of an hour. The G2 animals, it was administered a “bolus” of tramadol on the basis of 4,0 mg/kg, intravenous via, shortly after the anesthesic induction with propofol. It was assessed both cardiac and respiratory frequencies, rectal temperature, sedation, orotraqueal induction, analgesia, arterial pressures (systolic, diastolic and average), oxihemoglobine saturation, protective reflexes, cortisol dosage and recovery (extubation time, time for esternal decubitus and time for a four-footed standing), among the groups, within each moment. Both cardiac and respiratory frequencies besides the cortisol dosage showed significative differences (P<0,05) among the moments. The rectal temperature showed significative effect (P<0,05) in the interaction among groups and moments. The arterial pressures (systolic, diastolic and average) showed substantial differences (P<0,05) among groups and moments. The protective reflexes (ocular, eye-lids and rectal), showed substantial differences (P 0,05) among the groups, as well the time of extubation, one of the parameters of recovery. Sedation, orotraqueal intubation, analgesia, oxihemoglobine saturation, time for esternal decubitus and time for four-footed standing, did not present significative differences (P>0,05) among groups and nor among moments.

Made available in DSpace on 2014-06-11T19:23:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-10-20Bitstream added on 2014-06-13T20:28:10Z : No. of bitstreams: 1 doria_rgs_me_jabo.pdf: 844929 bytes, checksum: 66ab2b4d51e336752ba5ac561a267860 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Avaliaram-se, 8 equinos, sob anestesia geral inalatoria com isofluorano (1CAM) e infusao continua de xilazina (0,35mg/kg/h) ou medetomidina (3,5£gg/kg/h), em relacao a frequencia cardiaca, ritmo cardiaco, frequencia respiratoria, pressao arterial, hemogasometria arterial, tonus muscular e temperatura, nos tempos T0 (imediatamente antes do inicio da infusao continua) e T10 ao T60 (intervalos de 10 minutos, apos inicio da infusao continua), alem da qualidade da tranquilizacao, inducao e recuperacao anestesica. Os dados parametricos foram submetidos a analise de variancia para repeticoes multiplas, seguido pelo teste de Student-Newman-Keuls e, entre os grupos, teste-t de Student. Para os dados nao parametricos utilizou-se teste de Friedman e entre os grupos, teste de Mann-Whitney (p-T0,05). Houve reducao da frequencia cardiaca e da temperatura e elevacao da pressao arterial media. A paCO2 (no GM) e a ctCO2 elevaram-se e a paO2 mostrou-se maior no GM que no GX. Os dois farmacos mostraram-se eficientes para tranquilizacao, mas o GM demonstrou melhor miorrelaxamento e qualidade de inducao anestesica que o GX. Da mesma forma, a recuperacao anestesica apresentada pelo GM foi de melhor qualidade, embora mais prolongada. Conclui-se que a infusao continua de doses equipotentes de xilazina e medetomidina, durante anestesia geral inalatoria, com isofluorano, em equinos, promove alteracoes cardiocirculatorias, respiratorias e hemogasometricas discretas e equivalentes. / Eight equines under inhalatory general anesthesia with isoflurane (1MAC) and continuous infusion of xylazine (0.35mg/kg/h) or medetomidine (3.5-Êg/kg/h) were evaluated for heart rate and rhythm, respiratory rate, arterial blood pressure, arterial blood gas analysis, muscle relaxation and temperature immediately before the beginning of the continuous infusion (T0) and in intervals of 10 minutes after the beginning of the continuous infusion (T10 to T60) and also for tranquillization, induction and anesthetic recovery quality. The parametric data were evaluated by one way repeated measures ANOVA, followed by Student-Newman-Keuls and between groups Student t-test. Non-parametric data were evaluated by Friedman test and between groups Mann-Whitney test (p.0.05). Heart rate and temperature decreased and mean Heart rate and temperature decreased and mean aaarrrttteeerrriiiaaalll ppprrreeessssssuuurrreee increased. PaCO2 (in GM) and ctCO2 increased and GM showed a higher paO2 than GX. Both drugs were efficient in tranquilization but GM showed better muscle relaxation and induction quality than GX. In the same way, GM presented better anesthetic recovery even though it took more time. We conclude that equipotent doses of continuous infusion of medetomidine and xylazine during inhalatory general anesthesia with isoflurane in equines promote slight and equivalent cardiocirculatory, respiratory and arterial blood gases changes.

Orientador: Carlos Augusto Araújo Valadão / Banca: Helenice de Souza Spinosa / Banca: Anderson Farias / Banca: Stelio Pacca Loureiro Luna / Banca: Antonio de Queiroz Neto / Resumo: Com base na ação do amitraz (AMZ) e da romifidina (RMF) em receptores alfa-2 adrenérgicos e nas possíveis vantagens da associação destes fármacos com agentes inalatórios para uma anestesia geral segura, compararamse os efeitos clínicos, cardiocirculatórios e hemogasométricos da infusão contínua (IC) de AMZ ou de RMF associada ao isofluorano. Relacionaram-se os efeitos observados à concentração plasmática do amitraz (CPA) e investigaram-se possíveis efeitos farmacodinâmicos do diluente lipídico (DIL) utilizado na sua formulação. A medicação pré-anestésica (MPA) intravenosa (IV) para cada grupo foi: RMF - 60 μg/kg; AMZ - 0,2 mg/kg; DIL - 60 μg/kg de RMF. Induziu-se a anestesia com midazolam (0,1 mg/kg IV) e cetamina S(+) (0,2 mg/kg IV). A manutenção foi feita com 1,3 V% de isofluorano associado às ICs (RMF - 60 μg/kg.h; AMZ - 0,2 mg/kg.h; DIL - 0,1 mL/kg.h) por 60 minutos. Um minuto após a MPA a CPA média foi 396 ng/mL, aumentando durante a IC (de 93 ng/mL para 257 ng/mL) e diminuindo na recuperação, atingindo 47 ng/mL em 60 minutos. A RMF causou boa sedação e indução, com intubação fácil; manteve a FC estável e aumentou gradualmente a PAM, alterando pouco o CO2; resultou em recuperação ideal. O AMZ causou sedação leve e manteve planos anestésicos mais superficiais do que a RMF, com hipotensão durante a IC; a indução e a intubação foram de boa qualidade; o miorrelaxamento foi maior do que com RMF; a recuperação não teve boa qualidade. O DIL não causou sedação e resultou em recuperação de má qualidade, sendo inerte em relação aos efeitos do AMZ. Concluiu-se que há possibilidade do uso clínico do AMZ, ficando indicados estudos complementares. / Abstract: Based on the action of amitraz (AMZ) and romifidine (RMF) on alpha-2 adrenergic receptors and in the possible advantages of combining them with inhalation anesthetics for a safe general anesthesia, the clinical, cardiocirculatory and hemogasometric effects of the continuous infusion (CI) of AMZ or RMF in association with isoflurane anesthesia were compared. The observed effects were related to the AMZ plasmatic levels (APL). The existence of pharmacodynamic effects of the lipid vehicle (LV) used for AMZ formulation was also investigated. The intravenous (IV) pre-anesthetic medications (PAM) were: RMF - 60 μg/kg; AMZ - 0.2 mg/kg; LV - 60 μg/kg de RMF. Anesthesia was inducted with midazolam (0.1 mg/kg IV) and S-ketamine (0.2 mg/kg IV) and maintained with 1.3 V% isoflurane, in association with the CIs (RMF - 60 μg/kg.h; AMZ - 0.2 mg/kg.h; LV - 0.1 mL/kg.h) for 60 minutes. One minute after PAM, APL was 396 ng/mL. During the CI, APL increased from 93 to 257 ng/mL. On recovery, APL decreased to 47 ng/mL in 60 minutes. With RMF there were good sedation and induction and the intubation was easy; HR was stable and MAP increased, with little CO2 alterations; the recovery was ideal. AMZ had less sedative effect and reached superficial anesthesia compared to RMF, with hypotension during CI; there were good induction and easy intubation; miorelaxation was greater with AMZ than with RMF; recovery was not good. The LV did not induce sedative effects and resulted in a poor recovery; it did not influence AMZ effects. The clinical use of AMZ is possible, but further studies are indicated. / Doutor

Os equinos são comumente anestesiados com agentes voláteis em procedimentos cirúrgicos acima de 60 minutos, resultando em depressão cardiovascular dosedependente, contribuindo para uma alta taxa de mortalidade. Sendo assim, este estudo objetivou determinar se o fentanil, em infusão contínua, seria capaz de diminuir a fração expirada de isoflurano, promovendo estabilidade cardiovascular transoperatória e uma melhor recuperação após cirurgia de artroscopia, em comparação à infusão de lidocaína ou quetamina, durante a manutenção da anestesia com isoflurano. Para tanto foram utilizados 20 equinos de 3 a 8 anos e pesando 350 a 500kg, submetidos a cirurgia de artroscopia em decúbito dorsal. Os animais foram divididos aleatoriamente em 4 grupos: GL (1,5 mg/kg em bolus e infusão de 0,15mg/kg/min) ; GQ (2mg/kg em bolus e infusão de 0,2mg/kg/min); GF (7&micro;g/kg em bolus e infusão de 0,7&micro;g/kg/min) e GI que não recebeu infusão de nenhum fármaco adjuvante. Foram avaliados os parâmetros cardiovasculares (FC, PAM, PAS e PAD), ventilatórios e de oxigenação (PaO2, PaCO2, Compl e Rva), fração expirada de isoflurano [ISSO](Fexp%), e qualidade de recuperação. Em relação à [ISSO] (Fexp%) as maiores quedas foram observadas no momento 30bolus em todos os grupos, que utilizaram adjuvantes, comparados ao momento basal sendo, GL (1,50 para 0,90%) GQ (1,44 para 0,96%) e GF (1,32 para 0,96%). Observou-se que após 15 minutos da interrupção da infusão contínua de fentanil e lidocaína a fração expirada de isoflurano foi aumentada GL 25% e GF 45%. Apesar de não ter havido diferença estatística, o GF apresentou escore de recuperação menor 16,8 pontos, GL 24,6; GQ 30,0 e GI 31,8 pontos. Conclui-se então que o uso do fentanil foi capaz de reduzir a fração expirada de isoflurano em até 43%, não observando qualquer efeito colateral no momento da recuperação após re-sedação com xilazina 0,5mg/kg. / Volatile anesthetics are commonly used in horse anesthesia in surgical procedures over 60 minutes, resulting in a dose-dependent cardiovascular depression, contributing to a high mortality rate. Thus, the aimed this study was determine whether fentanyl continuous rate infusion would be able to reduce end tidal isoflurane, promoting intraoperative cardiovascular stability and a better recovery after arthroscopic surgery, when compared to lidocaine or ketamine infusion during maintenance of anesthesia with isoflurane. Therefore, 20 horses aging 3-8 years and weighing 350 to 500 kg underwent arthroscopic surgery in dorsal recumbence. The animals were randomly divided into four groups: GL (1.5 mg/kg bolus and 0.15 mg/kg/min infusion rate of lidocaine), GQ (2 mg/kg bolus and 0.2 mg/kg/min infusion of ketamine); GF (7&micro;g/kg bolus and 0.7 mg/kg/min infusion rate of fentanyl) and GI did not receive any adjuvant infusion. Cardiovascular parameters (HR, MBP, SBP and DBP), ventilatory and oxygenation (PaO2, PaCO2, Cst and Rva), end tidal isoflurano [ISO] (Fexp%), and quality of recovery were evaluated. Regarding [ISO] (Fexp%) the highest decreases were observed at the time 30bolus in all groups with adjuvants, in comparison to base line -GL (1.50 to 0.90%) GQ (1.44 to 0.96 %) and GF (1.32 to 0.96%). At 15 minutes after the end of continuous rate infusion of fentanyl and lidocaine, expired fraction of isoflurane was increased 25% for GL and 45% for GF. Although there was no statistical difference, GF showed lower recovery score - 16.8 points, while 24.6 for GL, 30.0 for GQ and 31.8 points for GI. In conclusion, fentanyl was able to reduce end tidal isoflurane to 43%, with no side effects at recovery time after re-sedation with xylazine 0.5 mg / kg.

In critically ill patients, the pathophysiology of sepsis can affect the interactions between the antibiotic, the bacteria and the patient, leading to potential therapeutic failure and the development of antibiotic resistance. It is well acknowledged that research that optimises antibiotic exposure will assist improvement of outcomes in this patient group. Although beta-lactam antibiotics, such as piperacillin and meropenem, are commonly selected for empiric therapy of sepsis, dosing is unlikely to be optimal. In patients without renal dysfunction, data suggests that disease-induced alterations to pharmacokinetic parameters result in low trough concentrations for significant periods within a dosing interval. Administration of these time-dependent antibiotics by continuous infusion has been suggested to improve the pharmacokinetic-pharmacodynamic profile. Knowledge of concentrations in the extracellular fluid of human tissue, which is the target site of most pathogens, is particularly instructive. Extracellular fluid concentrations can be determined using techniques such as microdialysis. Therefore, the principal aims of this Thesis were to determine the plasma and subcutaneous tissue pharmacokinetics of piperacillin and meropenem administered by bolus dosing and continuous infusion in critically ill patients with sepsis; and to use Monte Carlo simulations to compare the ability of different dosing strategies to achieve pharmacodynamic endpoints. This Thesis also sought to compare the clinical outcomes of bolus dosing and continuous infusion of a beta-lactam antibiotic, ceftriaxone, in a prospective randomised controlled trial and to perform a meta-analysis on clinical outcomes from other similar published studies. Finally, this Thesis aimed to systematically review the published literature to determine any correlation between antibiotic dosing and the development of antibiotic resistance. The results of the pharmacokinetic studies, using piperacillin and meropenem, indicate that beta-lactam distribution into subcutaneous tissue, in critically ill patients with sepsis, is less than that observed in previous studies in healthy volunteers yet superior to studies in patients with septic shock. This supports the notion that the peripheral concentration of drugs may be inversely related to the level of sickness severity. Administration by continuous infusion was found to maintain statistically significantly higher trough beta-lactam concentrations in both plasma and subcutaneous tissue. Further analysis of the plasma data using population pharmacokinetic modeling and Monte Carlo simulations described significant pharmacodynamic advantages for administering meropenem or piperacillin by continuous infusion to organisms with high minimum inhibitory concentrations. Given the documented pharmacodynamic advantages for administering beta-lactams by continuous infusion, a prospective randomized controlled clinical trial was conducted using the beta-lactam antibiotic ceftriaxone. In 57 critically ill patients, we found equivalence between continuous infusion and bolus dosing in the intention-to-treat analysis. However, our a priori analysis criteria, requiring patients receive at least 4-days antibiotic treatment, found significant clinical and bacteriological advantages for administration by continuous infusion. To further investigate any clinical differences between bolus dosing and continuous infusion of beta-lactam antibiotics, we performed a meta-analysis of all published studies. Our analysis of the 13 published prospective randomized controlled trials (846 hospitalised patients) showed equivalence of continuous infusion and bolus dosing. Possible confounders observed within, and between the studies, make interpretation of these results challenging. However, two large retrospective cohorts not included in the meta-analysis, found definitive clinical and bacteriological advantages suggesting further research may be appropriate. The possible relationship between antibiotic dosing, or exposures, on the development of resistance was investigated using a structured review of the published literature. Our analysis of relevant papers found a wealth of data describing increasing levels of resistance with sub-optimal antibiotic dosing, particularly for fluoroquinolone antibiotics, but also for other classes including beta-lactams. These results demonstrate the importance of optimizing antibiotic dosing to decrease the development of antibiotic susceptibility from sub-optimal dosing, particularly for critically ill patients who are likely to have low drug concentrations. The results of this Thesis, suggest that a large, prospective, multi-centre randomised controlled trial in critically ill patients with sepsis, is required to definitively determine the clinical utility of administration of beta-lactam antibiotics by continuous infusion.

Submitted by Claudia Rocha (claudia.rocha@udesc.br) on 2018-02-16T11:12:33Z No. of bitstreams: 1 PGCA16MA187.pdf: 1684727 bytes, checksum: 5568c061fa23561e4110c551eb567400 (MD5) / Made available in DSpace on 2018-02-16T11:12:33Z (GMT). No. of bitstreams: 1 PGCA16MA187.pdf: 1684727 bytes, checksum: 5568c061fa23561e4110c551eb567400 (MD5) Previous issue date: 2016-02-19 / Capes / Chapter I: The aim of this study was to evaluate the analgesic effect of intraoperative and postoperative continuous infusion of ketamine in addition to their cardiovascular, blood gas and respiratory changes. 24 dogs were used, adult, with average weight and age of 19,2±10,1 kg and 8,5± 1,7 years, respectively. All animals were premedicated with 0,5 mg/kg of morphine and 0,02 mg/kg acepromazine by the IM route. Anesthesia was induced with propofol 4 mg/kg and maintenance of anesthesia with isoflurane 1 MAC, diluted in 100% oxygen, undergoing mechanical ventilation. Regarding analgesia during surgery the animals received after the induction, an initial bolus of fentanyl in a dose of 2,5 μg/kg by the IM route, followed by continuous infusion at the rate of 10 μg/Kg/h and then were divided into three groups: CP; received bonuses of ketamine at a dose of 2,5 mg/kg in the immediate postoperative and IC ketamine 10 μg/ kg/min in six hours postoperatively. The CTP; received bolus ketamine at a dose of 2,5 mg/kg after induction of anesthesia and IC ketamine 10 μg/ kg/min intraoperatively and ketamine 10 μg/ kg/min in six hours postoperative. And the SP; They received saline bolus after induction and in the immediate postoperative period, followed by saline IC in six hours postoperatively. Redemptions for analgesia, bradycardia and hypotension were performed with fentanyl, atropine and dobutamine, respectively. The surgical procedure was complete unilateral mastectomy, performed always by the same surgeon. Upon completion of the surgical procedure, all animals received meloxicam and morphine at a dose of 0,2 mg/kg and 0,5 mg/kg for IV and IM, respectively. The parameters were evaluated 10 minutes after induction of anesthesia (T0); 5 minutes after bolus injection of ketamine and / or fentanyl (T1); 15 minutes after bolus injection of ketamine and/or fentanyl (T2); After the skin incision (T3) and 30, 45, 60, 75 and 90 minutes after the start of the continuous infusion treatments (T4; T5; T6, T7 and T8). Yet they were recorded the total time of surgery and time to extubation in minutes. For algic animals were evaluated by an evaluator, prior to surgery (M0), 1 (M1), 2 (M2), 4 (M4), 6 (M6), 8 (M8), 12 (M12) and 24 ( M24) hours postoperatively. Morphine dose 0,5 mg/kg by the IM route, was standardized for painkillers redemptions when a score higher or equal to six points was observed, with the help of Pain Scale Composed of Glasgow. The incidence of sedation was evaluated in the same moments of pain assessment through the Adapted Sedation Scale Saponaro, 2014. There was a decrease of FC in T8 in the CP and SP in relation to the CTP. The PAS increased in CTP T3 to T8 and SP from T3 to T7 when compared to the time T0. The CTP decreased in PaCO2 between T2 and T8, relative to T0. The Cl- was higher in the T2 CTP when compared to the SP and the SP greater compared to CTP. Regarding the used sedation scale, there was no statistical difference for the sub item appearance. As for the sub item behavioral interaction significant differences were observed in M0 to M1, M2 and M4 in CP in M1 for CTP and M1 and M2 for the SP. The strength of the analysis, statistical differences were observed from M1 to M24 to the CP, M1 and M2 for the CTP and between M1 and M24 for the SP in relation to the M0 moment. And the answer to palm the M8 time, the SP and CP differed from the CTP showed values similar to those seen in CP and SP. In relation to the total sum of points for GCMPS significant differences were observed in relation to M0 between M1 and M24 to the CP, from M1 to M12 in CTP and M1 to M6 for the SP, and the M24 when the CP showed values different to those observed in SP. The survival curve analysis showed no statistical difference for the perioperative rescue with dobutamine and postoperative morphine between groups, with only difference to the rescue with intraoperative fentanyl, where the CTP group did not need any rescue. Chapter II: The experimental design was carefully similar to Chapter I, but after surgery there was no groups of division or distribution of treatments and the animals were placed in a single group. Thus aimed to evaluate the application of postoperative analgesic redemptions through the correlation of the Visual Analogue Scale (VAS) Glasgow Composite Measure Pain Scale (GCMPS), Acute Pain Scale at the University of Colorado (EDAUC) and University of Melbourne Pain Scale (UMPS) in bitches submitted to unilateral mastectomy full. The algic of the animals was performed with the aid of VAS, EDAUC, UMPS and GCMPS by two assessors, experienced and not experienced before surgery (M0), 1 (M1), 2 (M2), 4 (M4) 6 (M6), 8 (M8), 12 (M12) and 24 (M24) hours postoperatively. The analgesic rescue were performed with morphine 0,5 mg/kg by the IM route, when at least two of scale present a score greater than or equal to 50, 2, 9 and 6 respectively, and when the score was observed only by experienced assessor. There was an increase in the total sum of points for M1 to M12 pain score for the experienced assessor (E) and for non-experienced (NE) for the VAS. In the analysis of EDAUC higher values compared to M0 were observed between M2 to M8 for E and M1 to M12 to the NE. In GCMPS, higher pain scores were observed between M1 to M24 for E and M1 to M12 to the NE. In the analysis of UMPS the increase in the total sum of points for pain scores were evident from M1 to M24 for E and NE. The best overall correlation was 0,775 between GCMPS and EDAUC and among evaluators was 0,925 for GCMPS. Chapter I: We conclude that continuous infusion of ketamine promotes adequate cardiorespiratory stability and hemogasometric provides excellent additional analgesia in the perioperative period, but the administration of meloxicam and morphine in the immediate postoperative masked postoperative analgesic effects of ketamine, did there were differences in the application of analgesic rescues with morphine, will be shown between groups. Chapter II: We conclude that the pain scale Consisting of Glasgow, was more sensitive to detect the need for postoperative analgesic rescue bitches submitted to unilateral mastectomy full, requiring no prior experience by the evaluators to painful assessment / Capitulo I: O objetivo deste estudo foi avaliar o efeito analgésico transoperatório e pós-operatório da infusão contínua de cetamina, além de suas alterações cardiovasculares, hemogasométricas e respiratórias. Foram utilizadas 24 cadelas, adultas, com peso e idade médio de 19,2±10,1 Kg e 8,5±1,7 anos, respectivamente. Todos os animais foram pré-medicados com 0,5 mg/Kg de morfina e 0,02 mg/Kg de acepromazina pela via IM. A indução foi realizada com propofol 4 mg/Kg e a manutenção da anestesia com isoflurano 1 CAM, diluído em 100% de oxigênio, submetidos a ventilação mecânica. Quanto à analgesia transoperatória os animais receberam após a indução, um bolus inicial de fentanil na dose de 2,5 μg/Kg, pela via IV seguido da infusão contínua na taxa de 10μg/Kg/h e em seguida foram alocados em três grupos: o CP; receberam bolus de cetamina na dose de 2,5 mg/Kg no pós operatório imediato e IC de cetamina 10μg/Kg/min em seis horas de pós-operatório. O CTP; receberam bolus de cetamina na dose de 2,5 mg/Kg após a indução da anestesia e IC de cetamina 10μg/Kg/min no transoperatório e cetamina 10μg/Kg/min em seis horas de pós-operatório. E o SP; receberam bolus de salina após a indução e no pós-operatório imediato, seguido da IC de salina em seis horas de pós-operatório. Os resgates para analgesia, bradicardia e hipotensão foram realizados com fentanil, atropina e dobutamina, respectivamente. O procedimento cirúrgico foi de mastectomia total unilateral, realizado sempre pelo mesmo cirurgião. Ao término do procedimento cirúrgico, todos os animais receberam meloxicam e morfina na dose de 0,2 mg/Kg e 0,5 mg/Kg pela via IV e IM, respectivamente. Os parâmetros foram avaliados 10 minutos após a indução anestésica (T0); 5 minutos após o bolus de cetamina e/ou fentanil (T1); 15 minutos após o bolus de cetamina e/ou fentanil (T2); após a incisão de pele (T3) e 30, 45, 60, 75 e 90 minutos após o início da infusão contínua dos tratamentos (T4; T5; T6; T7 e T8). Ainda foram contabilizados o tempo total do procedimento cirúrgico e o tempo para extubação em minutos. Para avalição álgica os animais foram avaliados por um avaliador, antes da cirurgia (M0), 1 (M1), 2 (M2), 4 (M4), 6 (M6), 8 (M8), 12 (M12) e 24 (M24) horas de pós-operatório. A morfina na dose 0,5 mg/Kg, pela via IM, foi padronizada para os resgates analgésicos quando uma pontuação maior ou igual a seis pontos fosse observada, com o auxílio da Escala de dor Composta de Glasgow. A ocorrência de sedação também foi avaliada, nos mesmos momentos da avaliação da dor, por meio da Escala de Sedação Adaptada de Saponaro, 2014. Houve diminuição da FC em T8 no CP e no SP em relação ao CTP. A PAS aumentou no CTP de T3 a T8 e no SP de T3 a T7 quando comparados ao momento T0. A PaCO2 diminuiu no CTP entre T2 e T8, em relação ao T0. O Cl- foi maior no T2 em CTP quando comparado ao SP e maior no SP em relação ao CTP. Em relação a escala de sedação utilizada, não houve diferença estatística para o sub item aparência. Já para o sub item interação comportamental diferenças significativas em relação a M0 foram observadas em M1, M2 e M4 no CP, em M1 para o CTP e em M1 e M2 para o SP. Na análise da resistência, diferenças estatísticas foram observadas de M1 a M24 para o CP, M1 e M2 para o CTP e entre M1 e M24 para o SP em relação ao momento M0. E para a resposta à palma no momento M8, o CP diferiu do SP e o CTP apresentou valores semelhantes aos observados em CP e SP. Em relação ao somatório total de pontos pela GCMPS foram observadas diferenças significativas em relação ao momento M0 entre M1 e M24 para o CP, de M1 a M12 no CTP e de M1 a M6 para o SP, sendo que no momento M24 o CP apresentou valores diferentes aos observados em SP. Na análise da curva de sobrevivência não houve diferença estatística para o resgate transoperatório com dobutamina e pós-operatório com morfina entre os grupos, havendo apenas diferença para o resgate transoperatório com fentanil, onde o grupo CTP não necessitou de nenhum resgate. Capítulo II: O delineamento experimental foi criteriosamente semelhante ao do capítulo I, porém no pós operatório não houve divisão de grupos ou distribuição de tratamentos e os animais foram alocados em um único grupo. Desta forma, objetivou-se avaliar o requerimento de resgates analgésicos pós-operatórios por meio da correlação das Escala Analógica Visual (EVA), Escala de dor Composta de Glasgow (GCMPS), Escala de dor Aguda da Universidade do Colorado (EDAUC) e Escala de dor da Universidade de Melbourne (UMPS) em cadelas submetidas à mastectomia total unilateral. A avaliação álgica dos animais foi realizada com o auxílio da EVA, EDAUC, UMPS e GCMPS por meio de dois avaliadores, experiente e não experiente antes da cirurgia (M0), 1 (M1), 2 (M2), 4 (M4), 6 (M6), 8 (M8), 12 (M12) e 24 (M24) horas de pós-operatório. Os resgates analgésicos foram realizados com morfina 0,5 mg/Kg, pela via IM, quando ao menos duas das escalas apresentassem uma pontuação maior ou igual a 50, 2, 9 e 6 pontos respectivamente, e quando esta pontuação fosse observada apenas pelo avaliador experiente. Houve aumento no somatório total de pontos para o escore de dor de M1 a M12 para o avaliador experiente (E) e para o não experiente (NE) para a EVA. Na análise da EDAUC valores maiores em relação a M0 foram observados entre M2 a M8 para o E e de M1 a M12 para o NE. Na GCMPS, maiores escores de dor foram observados entre M1 a M24 para o E e de M1 a M12 para o NE. Já na análise da UMPS o aumento do somatório total de pontos para os escores de dor foram evidenciados entre M1 a M24 para o E e NE. A melhor correlação geral foi de 0,775 entre a GCMPS e a EDAUC e entre os avaliadores foi de 0,925 para a GCMPS. Capítulo I: Conclui-se que a infusão contínua de cetamina promove adequada estabilidade cardiorrespiratória e hemogasométrica, proporciona excelente analgesia adicional no período transoperatório, porém a administração do meloxicam e da morfina no pós-operatório imediato mascarou os efeitos analgésicos pós-operatórios da cetamina, pois não houve diferença no requerimento de resgates analgésicos com morfina, neste período entre os grupos. Capítulo II: Conclui-se que a Escala de dor Composta de Glasgow, foi mais sensível para detectar a necessidade de resgate analgésico pós-operatório em cadelas submetidas à mastectomia total unilateral, não exigindo experiência prévia pelos avaliadores para avaliação dolorosa

This thesis in the field of microdata analysis aims to introduce dose optimizing algorithms for the pharmacological management of Parkinson’s disease (PD). PD is a neurodegenerative disease that mostly affects the motor functions of the patients and it is characterized as a movement disorder. The core symptoms of PD are: bradykinesia, postural instability, rigidity, and tremor. There is no cure for PD and the use of levodopa to manage the core symptoms is considered the gold standard. However, long term use of levodopa causes reduced medication efficacy, and side effects, such as dyskinesia, which can also be attributed to overmedication. When that happens precise individualized dosing schedules are required. The goal of this thesis is to examine if algorithmic methods can be used to find dosing schedules that treat PD symptoms and minimize manifestation of side effects. Data from three different sources were used for that purpose: data from a clinical study in Uppsala University hospital in 2015, patient admission chart data from Uppsala University hospital during 2011-2015, and data from a clinical study in Gothenburg University during 2016-2017. The data were used to develop the methods and evaluate the performance of the proposed algorithms.The first algorithm that was developed was a sensor-based method that derives objective measurements (ratings) of PD motor states. The construction of the sensor index was based on subjective ratings of patients’ motor functions made by three movement disorder experts. This sensor-based method was used when deriving algorithmic dosing schedules. Afterwards, a method that uses medication information and ratings of the patients’ motor states to fit individual patient models was developed. This method uses mathematical optimization to individualize specific parameters of dose-effects models for levodopa intake, through minimizing the distance between motor state ratings and dose-effect curves. Finally, two different dose optimization algorithms were developed and evaluated, that had as input the individual patient models. The first algorithm was specific to continuous infusion of levodopa treatment, where the patient’s state was set to a specific target value and the algorithm made dosing adjustments to keep that patients motor functions on that state. The second algorithm concerned oral administration of microtables of levodopa. The ambition with this algorithm was that the suggested doses would find the right balance between treating the core symptoms of PD and, at the same time, minimizing the side effects of long term levodopa use, mainly dyskinesia. Motor state ratings for this study were obtained through the sensor index. Both algorithms followed a principle of deriving a morning dose and a maintenance dose for the patients, with maintenance dose being an infusion rate for the first algorithm, and oral administration doses at specific time points for the second algorithm.The results showed that the sensor-based index had good test-retest reliability, sensitivity to levodopa treatment, and ability to make predictions in unseen parts of the dataset. The dosing algorithm for continuous infusion of levodopa had a good ability to suggest an optimal infusion rating for the patients, but consistently suggested lower morning dose than what the treating personnel prescribed. The dosing algorithm for oral administration of levodopa showed great agreement with the treating personnel’s prescriptions, both in terms of morning and maintenance dose. Moreover, when evaluating the oral medication algorithm, it was clear that the sensor index ratings could be used for building patient specific models.

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2016-08-30T17:45:35Z No. of bitstreams: 1 2011 - Janh Carlo de Amorim Ferreira.pdf: 452426 bytes, checksum: 152fed7ea96dd8772e716b4b9f21b433 (MD5) / Made available in DSpace on 2016-08-30T17:45:35Z (GMT). No. of bitstreams: 1 2011 - Janh Carlo de Amorim Ferreira.pdf: 452426 bytes, checksum: 152fed7ea96dd8772e716b4b9f21b433 (MD5) Previous issue date: 2011-04-26 / This study was performed at Hospital de Cl?nicas Veterin?rias do Centro Universit?rio Pl?nio Leite Itabora?, Rio de Janeiro (Veterinary Hospital of Pl?nio Leite University, Itabora?, Rio de Janeiro) to monitor the hepatic biochemical profile of cats and their clinical parameters when submitted to continuous infusion of propofol at a 0,3 mg/kg/min dosage, for 90 minutes, and comparing to results obtained from cats who received continuous infusion of saline solution. Both groups were analyzed during a pre-determined period of time totalizing 28 days of observation and analysis. The following enzymes activity levels were determined: Aminotransferase (AST), Alanina-Aminotransferase (ALT), Gamma Glutamyl Transpeptidase (GGT) and Alkaline Fosfatasis (FA); serum levels of Albumin (A), Total Bilirrubin (BT) and Total Serum Proteins (PT), yet registering Respiratory (FR) and Heart Rate (FC), Systolic Blood Pressure (PAS), Mean Arterial Blood Pressure (PAM), Diastolic Blood Pressure (PAD) and Oxygen Partial Saturation (SPO2). Twenty healthy cats were analyzed on this study, their weights varying from two to four kilos and ages between three to five years old, submitted to experimental procedures performed during the months of January and February, 2010. The analysis of these results showed a major difference (p<0,05) between the ALT serum activities at the following positions: T2 (30 minutes), T3 (60 minutes), T5 (12 hours) and T9 (28 days); AST serum activities at T2, FA serum activities at T2, T6 (seven days) and T8 (21 days), emphasizing the fact only at this last position the GP levels were greater than GC; in the heart rate at T1 position (the beginning of this experiment), without compromising animals physical condition. None of the animals presented averages above parameters of normality. The other parameters examined did not present any significant differences, concluding that total intravenous anesthesia using continuous infusion of propofol was safe to contain cats in invasive surgical procedures, therefore providing more information regarding the safe use of this drug in animals. / O trabalho foi desenvolvido no Hospital de Cl?nicas Veterin?rias do Centro Universit?rio Pl?nio Leite, em Itabora?, RJ, com o intuito de monitorar perfil bioqu?mico hep?tico e par?metros cl?nicos de gatos submetidos ? infus?o cont?nua de propofol (GP) na dose de 0,3 mg/kg/min, durante 90 minutos, e comparando-se com resultados observados em gatos do grupo controle (GC), que receberam infus?o cont?nua de solu??o fisiol?gica. Os dois grupos foram avaliados em espa?os de tempo pr?-determinados, totalizando 28 dias de observa??es e an?lises. Foram determinadas as atividades s?ricas de aspartatoaminotransferase (AST), alanina-aminotransferase (ALT), gama-glutamil transpeptidase (GGT) e fosfatase alcalina (FA), determinadas as concentra??es s?ricas de Albumina (A), Bilirrubina total (BT) e Prote?nas Totais s?ricas (PT), registrando-se ainda as Frequ?ncias Respirat?rias (FR) e Card?acas (FC), Temperatura Retal (T), Press?es Arteriais Sist?licas (PAS), M?dias (PAM) e Diast?licas (PAD) e Satura??o parcial de O2 (SPO2). Foram utilizados no estudo 20 gatos h?gidos, com pesos variando entre dois e quatro kg e idades entre tr?s e cinco anos, que foram submetidos aos procedimentos experimentais no per?odo compreendido entre janeiro e fevereiro de 2010. A an?lise dos resultados demostraram que houve diferen?a significativa (p<0,05) nas atividades s?ricas de ALT nos momentos T2 (30 minutos), T3 (60 minutos), T5 (12 horas) e T9 (28 dias); nas atividades s?ricas de AST no momento T2; nas atividades s?ricas de FA nos momentos T2, T6 (7 dias) e T8 (21 dias), sendo que, somente neste ultimo momento as dosagens do GP foram maiores que no GC; na frequ?ncia card?aca no momento T1 (in?cio do experimento), sem causar qualquer comprometimento ? sa?de dos animais. Nenhum dos animais apresentou m?dias acima dos par?metros de normalidade. Os outros par?metros analisados n?o tiveram diferen?as significativas, concluindo-se que a anestesia intravenosa total com uso de propofol em infus?o cont?nua foi segura para conten??o de gatos em procedimentos incruentos, contribuindo assim para maiores informa??es em rela??o ao uso desse f?rmaco nesses animais